SIV infection of rhesus macaques serves as a valuable model for HIV infection in humans. Both viruses infect through the CD4 T-lymphocyte receptor, and are infectious and cytopathic for CD4+ T-lymphocytes and macrophages. The viruses are genetically closely related: SIV shares approximately 50 percent homology with HIV-1 and 80 percent homology with HIV-2. In SIV- infected rhesus macaques, as in HIV-infected humans, a predominantly asymptomatic infection is followed by a disease onset which is characterized by decreasing CD4+ T-lymphocytes, increasing susceptibility to opportunistic infections and increasing viral load. Due to the ability to challenge vaccinated macaques with live pathogenic virus, the SIV; rhesus macaque model system is invaluable in the development of HIV vaccines. In addition, the more rapid disease onset in this animal model (less than 2 years as opposed to l0 years with HIV infection in humans) enables vaccine efficacy to be determined relatively quickly (for review see: Gardner and Hu, l99l). Despite some success under ideal laboratory conditions, the development of a safe vaccine that will protect against SIV infection under more rigorous conditions has remained elusive. A complete vaccine would induce cytotoxic T lymphocytes (CTL) against the four major antigenic proteins in SIV, and humoral immunity against the envelope coat protein. Preliminary experiments in macaques have demonstrated that use of recombinant BCG can efficiently generate such antigen specific immunity,and this project will verify these results, as well as examine the other types of immunity resulting from immunizing with these vectors. It will also validate the use of a new biological adjuvant to serve as a safe boosting agent for the response.